Predictive biomarkers of pancreatic cancer metastasis: A comprehensive review

Abstract

This review provides a comprehensive overview of predictive biomarkers associated with metastasis in pancreatic cancer (PC), one of the most aggressive malignancies characterized by late-stage diagnosis and poor prognosis. Metastasis, particularly to the liver, lungs, and lymph nodes, significantly worsens patient outcomes by compromising organ function and promoting disease progression. Reliable biomarkers for predicting and detecting metastasis at early stages are critical for improving survival rates and guiding personalized therapies. This paper highlights both general and specific biomarkers, including genetic mutations, protein expression changes, and carbohydrate tumor markers such as CA19-9. Immunological factors, including PD-L1, inflammatory cytokines, and chemokines, further influence the metastatic process within the tumor microenvironment (TME). Specific biomarkers play pivotal roles in promoting metastasis through mechanisms such as epithelial-to-mesenchymal transition (EMT), tumor microenvironment remodeling, and immune evasion. Emerging markers such as circulating tumor cells (CTCs) and volatile organic compounds (VOCs) offer promising non-invasive tools for metastasis detection and monitoring. This review not only consolidates existing knowledge but also highlights the mechanisms through which specific biomarkers facilitate metastasis. Despite recent progress, challenges such as biomarker standardization, technical variability, and clinical validation remain, and addressing these hurdles is essential for integrating predictive biomarkers into clinical practice. Ultimately, this review contributes to advancing early detection strategies, personalized treatment options, and improved prognosis for PC patients.